Acute Peripheral Inflammation Increases Plasma Concentration of Hypoglycemic Agent Nateglinide with Decreased Hepatic Drug-Metabolizing Activity in Rats
| Autor: | Tetsuya Aiba, Moeko Kojina, Keiichiro Suzuki, Akane Nishiwaki |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Drug Male genetic structures media_common.quotation_subject Pharmaceutical Science Inflammation Nateglinide Pharmacology Carrageenan 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine CYP2C11 medicine Animals Hypoglycemic Agents Rats Wistar Incubation media_common chemistry.chemical_classification General Medicine Metabolism eye diseases Peripheral Rats acute inflammation 030104 developmental biology Enzyme chemistry hepatic drug metabolism nateglinide 030220 oncology & carcinogenesis Microsomes Liver medicine.symptom medicine.drug |
| Zdroj: | Biologicalpharmaceutical bulletin. 44(1) |
| ISSN: | 1347-5215 |
| Popis: | The effects of inflammation on hypoglycemic agents were evaluated in male rats with acute peripheral inflammation (API). Nateglinide (NTG) was utilized as a model compound, since it is a hepatically-metabolized compound and its metabolism is mainly mediated by CYP 2C11 enzyme. In the experiments, rats were subjected to carrageenan injection into their hind paws for API induction, and the plasma concentration profiles of NTG were then examined. In addition, pooled liver microsomes were prepared from control and API rats, and the hepatic drug-metabolizing activity toward NTG and the hepatic expression of CYP2C11 protein were evaluated. It was shown that the plasma concentration of NTG following its intravenous administration decreases at a slower rate in API rats than that in control rats. It was also indicated in the incubation study with the liver microsomes that the hepatic drug-metabolizing activity toward NTG decreases in API rats. Additionally, it was revealed in Western immunoblotting that the hepatic expression of CYP2C11 protein decreases in API rats. These findings suggest that inflammation occurring in peripheral tissues brings about a decrease in hepatic NTG metabolism by suppressing the hepatic expression of CYP2C11 protein, causing an alteration of the plasma concentration profile of NTG with its impaired elimination. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|